Alternative titles; symbols
ORPHA: 411641; DO: 1064;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 17p13.2 | Cystinosis, ocular nonnephropathic | 219750 | Autosomal recessive | 3 | CTNS | 606272 |
A number sign (#) is used with this entry because ocular nonnephropathic cystinosis is caused by mutation in the gene encoding cystinosin (CTNS; 606272), which maps to chromosome 17p13.
Ocular nonnephropathic cystinosis, a variant of the classic nephropathic type of cystinosis (219800), is an autosomal recessive lysosomal storage disorder characterized by photophobia due to corneal cystine crystals but absence of renal disease (summary by Anikster et al., 2000).
Lietman et al. (1966) observed a benign form of cystinosis in 3 affected sibs of cousin parents. The ages of the patients were 53, 50, and 42 years. Crystals of cystine were demonstrated in the cornea, buffy coat of the blood, and bone marrow. No amino aciduria or impairment of renal function was found. Cogan et al. (1958) described an asymptomatic adult with cystine demonstrable in cornea and bone marrow. Although the patients with adult cystinosis show characteristic crystals in the cornea, conjunctiva, circulating white cells and bone marrow, no evidence of renal tubular dysfunction is found. Some reported cases of familial crystalline corneal dystrophy may be examples of this condition. Deposits resembling those of cystinosis occur in the cornea in patients with dysproteinemia, such as in multiple myeloma (Burki, 1958).
Schneider et al. (1968) reported studies of 3 adult cystinosis cases. The intracellular deposits of free cystine appear to be unavailable for sustaining normal metabolism since fibroblasts from either the children or the adult type are not viable in a cystine-free medium. The intracellular content of cystine is lower in the adult form than in the childhood form, yet higher than in the heterozygote for the childhood form. Retinal lesions occur in the childhood form but not the adult form and may be responsible for the photophobia which is much more a feature of the childhood form. An abnormality in heterozygotes was demonstrated by Schneider et al. (1967) who found the concentration of free cystine to be about 6 times normal in the leukocytes of parents of patients. Brubaker et al. (1970) described brother and sister, aged 16 and 11 years, respectively. Since they had no proteinuria or other clinical abnormality, except for crystalline corneal deposits, their disorder fits the 'adult' type rather than the juvenile or adolescent type.
Anikster et al. (2000) identified 2 mild mutations in the CTNS gene, G197R (606272.0011) and IVS10-3C-G (606272.0009), in compound heterozygosity with severe mutations in this gene in patients with ocular nonnephropathic cystinosis. The mild mutations appear to allow for residual CTNS mRNA production, significant amounts of lysosomal cystine transport, and lower levels of cellular cystine compared with those in nephropathic cystinosis. Anikster et al. (2000) reported 4 additional individuals with ocular nonnephropathic cystinosis.
Anikster, Y., Lucero, C., Guo, J., Huizing, M., Shotelersuk, V., Bernardini, I., McDowell, G., Iwata, F., Kaiser-Kupfer, M. I., Jaffe, R., Thoene, J., Schneider, J. A., Gahl, W. A. Ocular nonnephropathic cystinosis: clinical, biochemical, and molecular correlations. Pediat. Res. 47: 17-23, 2000. [PubMed: 10625078] [Full Text: https://doi.org/10.1203/00006450-200001000-00007]
Brubaker, R. F., Wong, V. G., Schulman, J. D., Seegmiller, J. E., Kuwabara, T. Benign cystinosis: the clinical, biochemical and morphologic findings in a family with two affected siblings. Am. J. Med. 49: 546-550, 1970. [PubMed: 5477639] [Full Text: https://doi.org/10.1016/s0002-9343(70)80049-3]
Burki, E. A case of corneal changes in multiple myeloma (plasmacytoma). Ophthalmologica 135: 565-572, 1958. [PubMed: 13553265] [Full Text: https://doi.org/10.1159/000303353]
Burki, E., Rohner, M. Ein seltener Fall von kristalliner Hornhautdegeneration (A rare case of crystalline corneal degeneration). Ophthalmologica 129: 211-217, 1955. [PubMed: 14394617] [Full Text: https://doi.org/10.1159/000302518]
Cogan, D. G., Kuwabara, T., Hurlbut, C. S., McMurray, V. Further observations on cystinosis in the adult. JAMA 166: 1725-1726, 1958.
Lietman, P. S., Frazier, P. D., Wong, V. G., Shotton, D., Seegmiller, J. E. Adult cystinosis--a benign disorder. Am. J. Med. 40: 511-517, 1966. [PubMed: 5326434] [Full Text: https://doi.org/10.1016/0002-9343(66)90115-x]
Schneider, J. A., Bradley, K., Seegmiller, J. E. Increased cystine in leukocytes from individuals homozygous and heterozygous for cystinosis. Science 157: 1321-1322, 1967. [PubMed: 6038997] [Full Text: https://doi.org/10.1126/science.157.3794.1321]
Schneider, J. A., Wong, V. G., Bradley, K., Seegmiller, J. E. Biochemical comparisons of the adult and childhood forms of cystinosis. New Eng. J. Med. 279: 1253-1257, 1968. [PubMed: 4880015] [Full Text: https://doi.org/10.1056/NEJM196812052792303]